The overall aim of the proposed research program is to define, as far as possible, the factors which regulate respiration in the mature fetus and newborn, the transition at birth and the way in which this sequence is likely to be affected by hypoxia. The results are intended to form the basis of a more rational approach and treatment of respiratory difficulties in the newborn and in particular the cases of unaccountable death from respiratory failure in otherwise healthy infants. We propose three main groups of experiments. First, we shall identify, from experiments in mature exteriorized sheep fetuses, the level and type of central inhibition which renders respiratory and non-specific stimuli ineffective and we shall also attempt to identify the principal drive to ventilation in the fetus. By repeating these experiments in the newborn lamb, we shall identify the major changes in respiratory sensitivity which occur at birth. Secondly, we shall study the pattern of respiration in healthy newborn infants and lambs under various conditions of wakefulness and arousal and with computer assistance, we shall express the respiratory pattern in frequency terms and so assess its stability. We shall extend these studies in newborn lambs by creating chronic lesions in the afferent respiratory tracts and in newborn babies which have various forms of respiratory difficulty or other defects which cause chronic hypoxia. From all these results, we shall attempt to define the respiratory patterns in compact terms so that they may be useful for prognosis. Thirdly, we shall investigate in detail how respiratory neurones in sheep fetus and newborn lamb are affected by hypoxia and changes in the pH of brain extracellular fluid using appropriate microelectrodes and also the protective role of cerebral blood vessels and flow. From these results we shall estimate how vulnerable the brain, and in particular the medulla, is to the effects of hypoxia and in turn, how respiration before and after birth may be affected by the asphyxia which is a normal feature of labor, delivery and the birth process.